Introduction

This page introduces abnormalities associated with the integumentary system and its specializations. Note that each related page will also contain specific information for that component of this system.

Some Recent Findings

A novel homozygous deletion in EXPH5 causes a skin fragility phenotype[1] "Epidermolysis bullosa simplex (EBS) is the most common form of EB. Eight different genes have been implicated in the pathogenesis of different types of EBS, but a substantial portion of the cases cannot be attributed to mutations in known genes. Recently, recessive mutations in the gene EXPH5 (encoding exophilin-5, also known as Slac2-b) were identified in patients affected with a mild form of EBS. We used immunohistochemistry, Sanger sequencing and PCR-restriction fragment length polymorphism analysis to identify the cause of mild congenital skin fragility in a 3-year-old girl. No mutations were detected in KRT5 or KRT14, but we identified a novel homozygous deletion in EXPH5, which was found to cosegregate with the disease phenotype in the family."

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Cutis Aplasia

Cutis Aplasia (Image: NZ Crown copyright)

Congenital absence of the skin, particularly on the scalp, larger defects may extend to the dura or meninges. Generally isolated lesions, but can also be associated with a variety of other genetic disorders. Heals as a flat scar or keloid lump.

Ehlers-Danlos Syndrome

The main features of classic Ehlers-Danlos syndrome, which includes EDS I and EDS II, are loose-jointedness and fragile, bruisable skin that heals with peculiar scars. The syndrome is caused by mutation in the collagen gene. Infants are born prematurely due to premature rupture of fetal membranes.

Autosomal Recessive Congenital Ichthyosis

Congenital absence of the skin, particularly on the scalp, larger defects may extend to the dura or meninges. Generally isolated lesions, but can also be associated with a variety of other genetic disorders. Heals as a flat scar or keloid lump.

Incontinentia Pigmenti

"An X-linked dominant disorder with most but not all cases affecting females. The skin changes follow characteristic four stages. In the neonatal period the first stage is noted with blisters often preceded or accompanied by erythema. These involve any part of the body but usually not the face. They do not cross the midline. These lesions are best seen in the second photograph in the groin and suprapubic region. The lesions follow a linear distribution in the limbs and circumferentially around the trunk. Crops of lesions may occur over a period of weeks to few months. During that stage, peripheral eosinophilia may be noted. The second stage follows and is characterised by hyperkeratosis or verrucous changes. At times the 2 stages occur simultaneously as noted in the first and third photograph. The third stage is that of hyperpigmentation typically appearing as streaks or whorls. It may be present throughout childhood. The fourth stage seen in teenage or adults is that of pale or atrophic streaks. In the neonatal period, IP must be differentiated from herpetic lesions, bullous impetigo and epidermolysis bullosa." (Text and Images: NZ Crown copyright)

Mammary Glands

Gynecomastia is stimulation by maternal sex hormones leads to excessive development of newborn male mammary glands. There are several possible causes of this excess estrogen in boys which also causes musculoskeletal abnormalities (premature growth spurt, early fusion of epiphyses, and decreased adult height).

Breast Cancer

In 1994, two breast cancer susceptibility genes were identified

BRCA1 on chromosome 17

BRCA2 on chromosome 13

When an individual carries a mutation in either BRCA1 or BRCA2, they are at an increased risk of being diagnosed with breast or ovarian cancer at some point in their lives. Normal function of these genes was to participate in repairing radiation-induced breaks in double-stranded DNA. It is though that mutations in BRCA1 or BRCA2 might disable this mechanism, leading to more errors in DNA replication and ultimately to cancerous growth.

Breast Cancer Detection reduce mortality is through early detection (general screening of the population for BRCA1 and BRCA2 is not yet recommended). New strategies to find anti-cancer drugs are constantly being developed. The latest, called 'synthetic lethal screening' looks for new drug targets in organisms such as yeast and fruit flies. In the same way that studies in yeast recently helped to identify the functions of BRCA1 and BRCA2, it is thought that drugs that work in more primative organisms will also be applicable to humans.

The BreastScreen Australia monitoring report 2011-2012 presents the latest national statistics on this national screening program, which aims to reduce illness and death resulting from breast cancer through organised screening to detect cases of unsuspected breast cancer in women, thus enabling early intervention.

Around 55% of women in the target age group of 50-69 took part in the program, with more than 1.7 million women screening in 2011-2012.

Breast cancer mortality is at an historic low, at 44 deaths per 100,000 women.

Jaundice is the yellow color of skin (and mucous membranes) and is not an abnormality of the skin and is often seen in newborn infants. It is due to accumulation of bile pigments in blood and their deposition in body tissues.

Melanoma

Melanoma develops postnatally when melanocytes become malignantly transformed, these transformed cells can then become invasive and spread to other tissues. Melanocytes (neural crest) normally protect the postnatal skin cells against ultraviolet radiation (UV) damage. Both UV light and genetics related to skin colour have roles in melanoma susceptibility.

There are several different melanoma forms:

Superficial spreading - most common type of melanoma about 70% of all melanomas.

Nodular - about 15% of all melanomas and becomes invasive soon after first appearing.

Acral-lentiginous - about 8% of all melanomas and is the most common melanoma in dark-skinned people.